The announcement for the movie came from a fashion show where Ben Stiller and Owen Wilson walked down the runway, in character, as Derek and Hansel.
Eddie Murphy had expressed interest in being in this movie. He had even developed his own pose called "Black Iron".
Alexander Skarsgård, who played Meekus in Zoolander (2001), made a cameo appearance as "Adam" in this movie.
"Zoolander 2" marked the end of Stiller's long-standing tradition of starting his directorial efforts by bringing his cast and crew together and stepping on a glass bottle for good luck, a nod to the Jewish wedding tradition. When Stiller stepped on the glass bottle with his "Zoolander 2" team, he pierced the sole of his shoe and sliced his heel. Stiller called it "a harbinger of things to come for that movie."